Dominance of chemokine ligand 2 and matrix metalloproteinase-2 and -9 and suppression of pro-inflammatory cytokines in the epidural compartment after intervertebral disc extrusion in a canine model

BACKGROUND CONTEXT In canine intervertebral disc (IVD) disease, a useful animal model, only little is known about the inflammatory response in the epidural space. PURPOSE To determine messenger RNA (mRNA) expressions of selected cytokines, chemokines, and matrix metalloproteinases (MMPs) qualitatively and semiquantitatively over the course of the disease and to correlate results to neurologic status and outcome. STUDY DESIGN/SETTING Prospective study using extruded IVD material of dogs with thoracolumbar IVD extrusion. PATIENT SAMPLE Seventy affected and 13 control (24 samples) dogs. OUTCOME MEASURES Duration of neurologic signs, pretreatment, neurologic grade, severity of pain, and outcome were recorded. After diagnostic imaging, decompressive surgery was performed. METHODS Messenger RNA expressions of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF), interferon (IFN)γ, MMP-2, MMP-9, chemokine ligand (CCL)2, CCL3, and three housekeeping genes was determined in the collected epidural material by Panomics 2.0 QuantiGene Plex technology. Relative mRNA expression and fold changes were calculated. Relative mRNA expression was correlated statistically to clinical parameters. RESULTS Fold changes of TNF, IL-1β, IL-2, IL-4, IL-6, IL-10, IFNγ, and CCL3 were clearly downregulated in all stages of the disease. MMP-9 was downregulated in the acute stage and upregulated in the subacute and chronic phase. Interleukin-8 was upregulated in acute cases. MMP-2 showed mild and CCL2 strong upregulation over the whole course of the disease. In dogs with severe pain, CCL3 and IFNγ were significantly higher compared with dogs without pain (p=.017/.020). Dogs pretreated with nonsteroidal anti-inflammatory drugs revealed significantly lower mRNA expression of IL-8 (p=.017). CONCLUSIONS The high CCL2 levels and upregulated MMPs combined with downregulated T-cell cytokines and suppressed pro-inflammatory genes in extruded canine disc material indicate that the epidural reaction is dominated by infiltrating monocytes differentiating into macrophages with tissue remodeling functions. These results will help to understand the pathogenic processes representing the basis for novel therapeutic approaches. The canine IVD disease model will be rewarding in this process.

Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) among Swiss veterinary health care providers: detection of livestock- and healthcare-associated clones.

We screened a total of 340 veterinarians (including general practitioners, small animal practitioners, large animal practitioners, veterinarians working in different veterinary services or industry), and 29 veterinary assistants for nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus pseudintermedius (MRSP) at the 2012 Swiss veterinary annual meeting. MRSA isolates (n = 14) were detected in 3.8 % (95 % CI 2.1 - 6.3 %) of the participants whereas MRSP was not detected. Large animal practitioners were carriers of livestock-associated MRSA (LA-MRSA) ST398-t011-V (n = 2), ST398-t011-IV (n = 4), and ST398-t034-V (n = 1). On the other hand, participants working with small animals harbored human healthcare-associated MRSA (HCA-MRSA) which belonged to epidemic lineages ST225-t003-II (n = 2), ST225-t014-II (n = 1), ST5-t002-II (n = 2), ST5-t283-IV (n = 1), and ST88-t186-IV (n = 1). HCA-MRSA harbored virulence factors such as enterotoxins, β-hemolysin converting phage and leukocidins. None of the MRSA isolates carried Panton-Valentine leukocidin (PVL). In addition to the methicillin resistance gene mecA, LA-MRSA ST398 isolates generally contained additional antibiotic resistance genes conferring resistance to tetracycline [tet(M) and tet(K)], trimethoprim [dfrK, dfrG], and the aminoglycosides gentamicin and kanamycin [aac(6')-Ie - aph(2')-Ia]. On the other hand, HCA-MRSA ST5 and ST225 mainly contained genes conferring resistance to the macrolide, lincosamide and streptogramin B antibiotics [erm(A)], to spectinomycin [ant(9)-Ia], amikacin and tobramycin [ant(4')-Ia], and to fluoroquinolones [amino acid substitutions in GrlA (S84L) and GyrA (S80F and S81P)]. MRSA carriage may represent an occupational risk and veterinarians should be aware of possible MRSA colonization and potential for developing infection or for transmitting these strains. Professional exposure to animals should be reported upon hospitalization and before medical intervention to allow for preventive measures. Infection prevention measures are also indicated in veterinary medicine to avoid MRSA transmission between humans and animals, and to limit the spread of MRSA both in the community, and to animal and human hospitals.

Les Juifs de Russie : recueil d'articles et d'études sur leur situation légale, sociale et économique

[Mitarb.: E. B. Lanin, d.i. Valentine Dillon]

Dsh homolog DVL3 mediates resistance to IGFIR inhibition by regulating IGF-RAS signaling

Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibition was enhanced specifically in vitro and in vivo by genetic or pharmacologic blockade of DVL3. In breast and prostate cancer cells, sensitization tracked with enhanced MEK-ERK activation and relied upon MEK activity and DVL3 expression. Mechanistic investigations showed that DVL3 is present in an adaptor complex that links IGFIR to RAS, which includes Shc, growth factor receptor-bound-2 (Grb2), son-of-sevenless (SOS), and the tumor suppressor DAB2. Dual DVL and DAB2 blockade synergized in activating ERKs and sensitizing cells to IGFIR inhibition, suggesting a nonredundant role for DVL3 in the Shc-Grb2-SOS complex. Clinically, tumors that responded to IGFIR inhibition contained relatively lower levels of DVL3 protein than resistant tumors, and DVL3 levels in tumors correlated inversely with progression-free survival in patients treated with IGFIR antibodies. Because IGFIR does not contain activating mutations analogous to EGFR variants associated with response to EGFR inhibitors, we suggest that IGF signaling achieves an equivalent integration at the postreceptor level through adaptor protein complexes, influencing cellular dependence on the IGF axis and identifying a patient population with potential to benefit from IGFIR inhibition.

Stabilizing Lead Cathodes with Diammonium Salt Additives in the Deoxygenation of Aromatic Amides

Lead is efficiently protected against cathodic corrosion by the addition of diammonium salts in the electrolyte. The cationic coating of the cathode allows the efficient electroreduction of benzamides to benzylamines. The electrochemical deoxygenation of the amide is achieved without the use of oxophilic agents or sacrificial anodes. The surface of the lead cathode stays smooth and the cathode can be reused for multiple runs, providing <2.5 ppm of the crude product. Cyclic voltammetry studies reveal a shift in the onset potential of the hydrogen evolution reaction by −157 mV.

High-Resolution Chemical Depth Profiling of Solid Material Using a Miniature Laser Ablation/Ionization Mass Spectrometer

High-resolution chemical depth profiling measurements of copper films are presented. The 10 μm thick copper test samples were electrodeposited on a Si-supported Cu seed under galvanostatic conditions in the presence of particular plating additives (SPS, Imep, PEI, and PAG) used in the semiconductor industry for the on-chip metallization of interconnects. To probe the trend of these plating additives toward inclusion into the deposit upon growth, quantitative elemental mass spectrometric measurements at trace level concentration were conducted by using a sensitive miniature laser ablation ionization mass spectrometer (LIMS), originally designed and developed for in situ space exploration. An ultrashort pulsed laser system (τ ∼ 190 fs, λ = 775 nm) was used for ablation and ionization of sample material. We show that with our LIMS system, quantitative chemical mass spectrometric analysis with an ablation rate at the subnanometer level per single laser shot can be conducted. The measurement capabilities of our instrument, including the high vertical depth resolution coupled with high detection sensitivity of ∼10 ppb, high dynamic range ≥10(8), measurement accuracy and precision, is of considerable interest in various fields of application, where investigations with high lateral and vertical resolution of the chemical composition of solid materials are required, these include, e.g., wafers from semiconductor industry or studies on space weathered samples in space research.

High depth-resolution laser ablation chemical analysis of additive-assisted Cu electroplating for microchip architectures

Laser ablation/ionisation mass spectrometry with a vertical resolution at a nanometre scale was applied for the quantitative characterisation of the chemical composition of additive-assisted Cu electroplated deposits used in the microchip industry. The detailed chemical analysis complements information gathered by optical techniques and allows new insights into the metal deposition process.

Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands

4-Aryl-1,1,1-trifluorobut-3-en-2-ones ArCH[double bond, length as m-dash]CHCOCF3 (CF3-enones) react with arenes in excess of Brønsted superacids (TfOH, FSO3H) to give, stereoselectively, trans-1,3-diaryl-1-trifluoromethyl indanes in 35-85% yields. The reaction intermediates, the O-protonated ArCH[double bond, length as m-dash]CHC(OH(+))CF3 and the O,C-diprotonated ArHC(+)CH2C(OH(+))CF3 species, have been studied by means of (1)H, (13)C, (19)F NMR, and DFT calculations. Both types of the cations may participate in the reaction, depending on their electrophilicity and electron-donating properties of the arenes. The formation of CF3-indanes is a result of cascade reaction of protonated CF3-enones to form chemo-, regio- and stereoselectively three new C-C bonds. The obtained trans-1,3-diaryl-1-trifluoromethyl indanes were investigated as potential ligands for cannabinoid receptors CB1 and CB2 types. The most potent compound showed sub-micromolar affinity for both receptor subtypes with a 6-fold selectivity toward the CB2 receptor with no appreciable cytotoxicity toward SHSY5Y cells.

Editorial genesis: From comparing texts (product) to interpreting rewritings (process)

In literary genetics, “editorial genetics” deals with the “public life” of texts, whereas the writing process is affected by edition and diffusion. Editorial genetics frequently has to deal with cases of “editorial rewriting”: in the literary domain for example, authors frequently modify previously published works, so that several versions may co-exist. We are especially interested in Balzac’s La Bourse (translated in English as The Purse) since we know three authorized versions of this specific work.By comparing different texts associated with a single work, the literary geneticist is facing different products that are themselves the result of a writing process. However, different specificities should be outlined: (1) the writing process does not leave any trace: we just have access to different products/texts and (2) since the texts we compare seem to be achieved, differences must be referred, not to programmatic or temporary linguistic structures, but to the reconfiguration of a pre-existing textuality.Do such products still reflect the processes that have given birth to them? Does the comparison between two texts considered as variations of a same text give access to this transformation’s processes? After describing the objects of this particular textual comparison and the terminology that permits to give an account of such phenomenon, this contribution suggests to express these questions differently, as a matter of poetics of transitions between texts, or, further digging, an hermeneutics of the transition between texts.

Dielectrophoresis-based analyte separation and analysis

Dielectrophoresis—the tendency of a material of high dielectric permittivity to migrate in an electrical field gradient to a region of maximum field strength—provides an ideal motive force for manipulating small volumes of biological analytes in microfluidic microsystems. The work described in this thesis was based on the hypothesis that dielectrophoresis could be exploited to provide high-resolution cell separations in microsystems as well as a means for the electrically-controllable manipulation of solid supports for molecular analysis. To this end, a dielectrophoretic/gravitational field-flow-fractionation (DEP/G-FFF) system was developed and the separation performance evaluated using various types and sizes of polystyrene microspheres as model particles. It was shown that separation of the polystyrene beads was based on the differences in their effective dielectrophoretic properties. The ability of an improved DEP/G-FFF system to separate genetically identical, but phenotypically dissimilar cell types was demonstrated using mixtures of 6m2 mutant rat kidney cells grown under transforming and non-transforming culture conditions. Additionally, a panel of engineered dielectric microspheres was designed with specific, predetermined dielectrophoretic properties such that their dielectrophoretic behaviors would be controllable and predictable. The fabrication method involved the use of gold-coated polystyrene microsphere cores coated with a self-assembled monolayer of alkanethiol and, optionally, a self-assembled monolayer of phospholipid to form a thin-insulating-shell-over-conductive-interior structure. The successful development of the DEP/G-FFF separation system and the dielectrically engineered microspheres provides proof-of-principle demonstrations of enabling dielectrophoresis-based microsystem technology that should provide powerful new methods for the manipulation, separation and identification of analytes in many diverse fields. ^

Na 1 Nachlass Max Horkheimer, 103 - Korrespondenzen u.a. mit Maria Pattermann und Franz Neumann (p. III 11, 1-335)

1 Drucksache der Rechtsanwaltskanzlei Pacht, Tannenbaum & Ross, 1951; 2 Briefe zwischen der Pädagogischen Hauptstelle der Gewerkschaft Erziehung u. Wissenschaft und Max Horkheimer, 1954; 1 Brief vom Pädagogischen Verlag B. Schulz an Max Horkheimer, 1950; 3 Briefe zwischen dem Professor Erwin Walter Palm und Max Horkheimer, 1957-1958; 2 Briefe zwischen Helena Brans und Max Horkheimer, 1953; 2 Briefe vom Park-Hotel Frankfurt an Max Horkheimer,1957-1958; 1 Brief von Enno Patalas an Max Horkheimer, 1 Brief von Theodor W. Adorno an Enno Patalas, 1956; 2 Briefe zwischen Dieter Pätzold und Max Horkheimer, 1952; 8 Briefe zwischen Maria Pattermann und Max Horkheimer, 1952-1958; 2 Briefe zwischen F. Perrot und Max Horkheimer, 1953; 2 Briefe zwischen der Buchhandlung Werner Peter und Max Horkheimer, 1954; 3 Briefe zwischen Alfred Peters und Max Horkheimer, 1952-1953; 1 Zeugnis von dem Studenten Joachim Peter, 1953; 1 Brief von Max Horkheimer an F.H. Peterson, 1950; Briefwechsel zwischen dem Studenten Klaus Peuker und Max Horkheimer, 1951; 1 Brief des Chefredakteuren Karl Pfannkuch an Max Horkheimer, 1955; 1 Brief von Dr. Karl Pfauter an Max Horkheimer, 1952; Briefwechsel zwischen der Studentin Renate Pflaume und Max Horkheimer, 1952; Briefwechsel zwischen Joseph B. Phillips und Max Horkheimer, 1955; 1 Brief von Professor Josef Pieper an Max Horkheimer , 1951; 1 Brief von Ehrenfried Pihan an Max Horkheimer, 1953; 1 Brief von F. G. Pincus an Theodor W. Adorno, 1954; Briefwechsel zwischen dem Professor Koppel S. Pinson und Max Horkheimer, 1956; 2 Briefe zwischen dem Professor Kurt Pinthus und Max Horkheimer, 1953; 1 Brief an Dr. Knut Pipping von Max Horkheimer, 1950; 2 Briefe zwischen Erwin Piscator und Max Horkheimer, 1954; Briefwechsel zwischen der Max-Planck-Gesellschaft zur Förderung der Wissenschaften und Max Horkheimer, 1953-1955; Briefwechsel zwischen dem Professor Richard Plant und Max Horkheimer, 1953 und 2 Briefe zwischen Professor Richard Plant und Margarete Feretty-Füredi, 1953; Briefwechsel zwischen dem Professor Johann Plenge und Max Horkheimer, 1951-1952; Briefwechsel zwischen Barbara Pleyer und Max Horkheimer, 1954; 1 Brief von Erich Paul Pechmann an Max Horkheimer, 1952; Briefwechsel zwischen Dr. Gerhard Poetzsch und an Max Horkheimer, 1958; Briefwechsel zwischen dem Committee on Science & Freedom und Max Horkheimer, 1955-1956; 1 Brief an den Professor Rudolf Pohl von Max Horkheimer, 1953; 1 Brief von der Zeitschrift "Die politsche Meinung" an Max Horkheimer, 1956; 1 Brief von Max F. Pollack an Max Horkheimer, 1954; 1 Brief von dem Professor Wilhelm Polligkeit an Max Horkheimer, 1951; 1 Brief von dem Poli-Verlag an Max Horkheimer, 1950; Briefwechsel zwischen Alexej Poremsky und Max Horkheimer, 1955; 1 Brief von Rita Post an Max Horkheimer, 1952; 1 Brief von Max Potzin an Max Horkheimer, 1951; Briefwechsel zwischen dem Oberstudienrat Max Preitz und Max Horkheimer, 1955; 1 Brief von dem Professor Wolfgang Preiser an Max Horkheimer, 1952; 1 Gutachten und Beilagen von Dr. Karl A. Preuschen an Max Horkheimer, 1955; Briefwechsel und Beilagen zwischen dem Direktor des The Commonwealth Fund E. K. Wickman und Max Horkheimer, 1955; Briefwechsel zwischen Klaus H. Pringsheim und Max Horkheimer, 1952-1958; 1 Brief von Curt Freiherr von Preuschen an Max Horkheimer, 1953; Briefwechsel zwischen Rüdiger Proske und Max Horkheimer, 1951; Briefwechsel und Beilagen zwischen Dr. Harry Pross und Max Horkheimer, 1954; 1 Brief von dem Professor Franz Neumann an Max Horkheimer, 1954; 1 Brief an G. H. Graber von Max Horkheimer, 1953; Briefwechsel zwischen dem Quaker Service und Max Horkheimer, 1950; Briefwechsel zwischn Günther Quandt und Max Horkheimer, 1953 und 2 Todesanzeigen, 1955; 1 Brief an den Querido-Verlag von Max Horkheimer, 1951; Briefwechsel zwischen Emil Querinjean und Max Horkheimer, 1955; Briefwechsel zwischen John Raatjes und Max Horkheimer, 1956; Briefwechsel zwischen der Zeitschrift the humanist radical und Max Horkheimer, 1957; Briefwechsel zwischen Sitangghu Chatterji und Max Horkheimer, 1957; 1 Brief von der Radio Corporation of America an Max Horkheimer, 1953; 1 Brief und Beilagen vom Radiodiffusion et Télévision Francaises an Max Horkheimer, 1955; Briefwechsel zwischen dem Österreichischer Rundfunk Radio Wien und Max Horkheimer, 1956; 1 Brief von dem Professor Boris Rajewsky an Max Horkheimer, 1953; 1 Brief an Else Rang von Max Horkheimer, 1950; Briefwechsel zwischen Heinz Raspini und Max Horkheimer, 1956; 1 Drucksache zwischen Hanna Becker vom Rath und Max Horkheimer, 1953; 1 Telegramm von dem Professor Roland Rather an Max Horkheimer und 2 Briefe von Max Horkheimer an Roland Rather, 1957; Briefwechsel zwischen dem Professor L. J. Rather und Max Horkheimer, 1955; Briefwechsel zwischen Phillip Roth und Max Horkheimer, 1958; Briefwechsel zwischen Sibnarayan Ray und Max Horkheimer, 1956-1957; Briefwechsel mit Beilagen zwischen dem Rationalisierungs-Kuratorium der Deutschen Wirtschaft und Max Horkheimer, 1954; 1 Aktennotiz von dem Jornalisten Rasten der dänischen Zeitung Politiken, 1953; Briefwechsel zwischen Wolfgang M. Rauch und Max Horkheimer, 1956; 1 Anzeige der Ingeborg Rauter, 1953; 1 Brief von dem Hotel Reber au lac an Max Horkheimer, 1955; Briefwechsel zwischen Alice Reboly und Max Horkheimer, 1955; 3 Briefe an die Regensburger Zeitungen von Max Horkheimer, 1956; 1 Brief an den Professor Klaus Reich von Max Horkheimer, 1950; Briefwechsel zwischen dem Reinhardt, Ernst, Verlag und Max Horkheimer, 1953; 1 Brief von dem Apotheker Hermann Reitberger an Max Horkheimer, 1955; Briefwechsel zwischen Dr. Paul Reiwald und Max Horkheimer, 1950; 1 Brief von dem Journalist Godo Remszhardt an Max Horkheimer, 1954; Briefwechsel zwischen Dr. Irmgard Rexroth-Kern und Max Horkheimer, 1952; Briefwechsel zwischen Hans Rheinbay und Max Horkheimer, 1955; 1 Brief von der Universität Bonn an Max Horkheimer, 1953; 1 Brief an den Rheinischer Merkur von Max Horkheimer, 1951; 1 Brief an die Rheinische Post von Max Horkheimer, 1954; 1 Brief an Hans Richter von Max Horkheimer, 1954; Briefwechsel zwischen Dr. Hermann Riefstahl und Max Horkheimer, 1957; Briefwechsel zwischen dem Professor Svend Riemer und Max Horkheimer, 1957; Briefwechsel zwischen dem Ring-Verlag und Max Horkheimer, 1957; Briefwechsel zwischen Werner Rings und Max Horkheimer, 1954; Briefwechsel zwischen Martha Ritter-Raabe und Max Horkheimer, 1955; Briefwechsel zwischen Otto-Heinz Rocholl und Max Horkheimer, 1954; 1 Brief von Hilde Rodemann an Max Horkheimer, 1952; 1 Brief von Edouard Roditi an Max Horkheimer, 1951 und 1 Brief von Theodor W. Adorno an Edouard Roditi, 1951; Briefwechsel zwischen der Zeitschrift Studenten-Kurier und Max Horkheimer, 1955; 1 Brief von Karl Roeloffs an Max Horkheimer, 1953; Briefwechsel zwischen der Kunsthistorikerin Hanna Rhode und Max Horkheimer, 1950-1951; 1 Brief an Dr. Anna Ronge von Max Horkheimer, 1954; 2 Brief an Kathe Romney von Max Horkheimer, 1952-1955; Briefwechsel zwischen Dr. Paul Rompel und Max Horkheimer, 1952; 1 Brief an den Zahnartz Dr. Ingo Ropper von Max Horkheimer, 1953; Briefwechsel zwischen Ilse Wallis Ross und Max Horkheimer, 1955-1956; 1 Brief von dem Professor Hans W. Rosenhaupt an Max Horkheimer, 1952; 1 Brief von Rosenthal an Max Horkheimer, 1958; Briefwechsel zwischen dem Generalstaatsanwalt und Staatssekretär Erich Rosenthal-Pelldram und Max Horkheimer, 1952-1956; Briefwechsel zwischen Lessing J. Rosenwald und Max Horkheimer, 1950; Briefwechsel zwischen dem Lieutenant Dr. Alan O. Ross und Max Horkheimer, 1955; 4 Briefe und Beilagen von Günther Roth an Max Horkheimer, 1953-1957; Briefwechsel zwischen dem Professor Wolfram Eberhardt und Max Horkheimer, 1955; 1 Brief an den Professor M. A. Stewart von Theodor W. Adorno, 1955; Briefwechsel zwischen dem Professor Rheinhard Bendix und Max Horkheimer, 1955; Briefwechsel zwischen der Studentin Valentine Rothe und Max Horkheimer, 1957; 1 Brief von dem Student Rudolf Rothrock an Max Horkheimer, 1953; 1 Brief von Guy Roustang an Max Horkheimer, ohne Jahr; 1 Brief von Heinz Maria Ledig-Rowohlt an Max Horkheimer, 1950; Briefwechsel zwischen Ellen Roy und Max Horkheimer, 1956; Briefwechsel zwischen dem Professor Paul Royen und Max Horkheimer, 1954; Briefwechsel zwischen dem Staatsminister August Rucker und Max Horkheimer, 1955-1957 1 Brief an den Staatsminister August Rucker von Leopold von Wiese, 1955; 1 Bericht von Walter Rüegg, 1953 und 2 Briefe von Max Horkheimer an den Professor Walter Rüegg, 1955; 3 Briefe an den Professor Alexander Rüstow von Max Horkheimer, 1953-1958; Briefwechsel zwischen Käthe von Ruckteschell und Max Horkheimer, 1951-1954; Briefwechsel zwischen dem Student Gerhard Rudolph und Max Horkheimer, 1954; 1 Brief von der Ruf und Echo, Arbeitsgemeischaft an Max Horkheimer, 1952; 3 Briefe an den Professor Jay Rumney von Max Horkheimer, 1952-1954; Briefwechsel zwischen Clarence R. Rungee und Max Horkheimer, 1951-1952;